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Updated: Jun 16, 2025
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
Single-cell transcriptomics identify a chemotherapy-resistance related cluster overexpressed CLIC3 in ovarian cancer
Zhefeng Li1, Jie Li1,2, Yue Li1
1Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 100026, China.
Background:
Chemoresistance, the primary cause of mortality among ovarian cancer (OC) patients, is a multifaceted process encompassing numerous biological phenomena. As sequencing technology continues to advance, single-cell sequencing has surfaced as a potent strategy to elucidate the pathogenesis of OC.
Methods:
We examined single-cell sequencing data derived from five OC samples (three resistant and two sensitive) and identified an epithelial subcluster associated with chemotherapy resistance and poor prognosis. Using GSVA and cell communication analysis, we explored the unique biological functions and communication characteristics of this resistant subcluster. We performed high dimensional weighted gene co-expression network analysis and differential expression analysis to identify the hub genes of c3. Lastly, we investigated the correlation between the hub gene, CLIC3, and chemotherapy drug sensitivity. We also validated their involvement in specific pathways using TCGA data. The effects and primary mechanism to chemoresistance of CLIC3 was explored.
Results:
We identified a cell subcluster, denoted as c3, strongly linked to chemoresistance and poor prognosis in OC. This subcluster demonstrated a correlation with both extracellular matrix (ECM) formation and angiogenesis signature, with CLIC3 identified as its key marker. The expression levels of CLIC3 exhibit a significant association with the sensitivity to various chemotherapeutic drugs in OC. Mechanistically, CLIC3 increases OC resistance to cisplatin by promoting integrin β1 redistribution and PI3K-AKT pathway.
Conclusions:
This study offers a novel insight into the progression and chemoresistance of OC. Additionally, we identified a specific cell cluster highly associated with chemoresistance. The marker for this cluster, CLIC3, increases OC resistance to cisplatin by promoting integrin β1 redistribution and PI3K-AKT pathway and holds significant potential as a new therapeutic target for OC.
Insights
Chemoresistance in ovarian cancer (OC) is linked to a specific cell subcluster (c3). The marker CLIC3 drives cisplatin resistance by affecting cell signaling pathways, offering a potential new therapeutic target for OC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Chemoresistance is a major cause of mortality in ovarian cancer (OC).
- Single-cell sequencing offers insights into OC pathogenesis and chemoresistance.
- Understanding chemoresistance mechanisms is crucial for improving patient outcomes.
Purpose of the Study:
- To identify cellular mechanisms underlying chemoresistance in ovarian cancer.
- To investigate the role of specific cell subclusters and their markers in OC chemoresistance.
- To explore CLIC3 as a potential therapeutic target for overcoming chemoresistance.
Main Methods:
- Analysis of single-cell sequencing data from OC samples (resistant and sensitive).
- Identification of chemoresistance-associated cell subclusters using GSVA and cell communication analysis.
- Gene co-expression network analysis and differential expression analysis to identify hub genes, including CLIC3.
- Validation of CLIC3's role and mechanism in chemoresistance using TCGA data.
Main Results:
- A distinct cell subcluster (c3) was identified, correlating with chemoresistance and poor prognosis in OC.
- CLIC3 was identified as the key marker for this subcluster, associated with extracellular matrix formation and angiogenesis.
- CLIC3 expression levels significantly correlate with sensitivity to various chemotherapeutic drugs.
- CLIC3 promotes cisplatin resistance by enhancing integrin β1 redistribution and activating the PI3K-AKT pathway.
Conclusions:
- A novel cell cluster (c3) associated with OC chemoresistance was identified.
- CLIC3 is a key marker for this cluster and significantly contributes to cisplatin resistance.
- CLIC3's mechanism involves integrin β1 redistribution and the PI3K-AKT pathway, highlighting its potential as a therapeutic target for OC.
